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@ARTICLE{Ovesen:276822,
      author       = {Ovesen, Peter Lund and Juul-Madsen, Kristian and Telugu,
                      Narasimha S and Schmidt, Vanessa and Frahm, Silke and
                      Radbruch, Helena and Louth, Emma Louise and Korshøj, Anders
                      Rosendal and Heppner, Frank L and Diecke, Sebastian and
                      Kettenmann, Helmut and Willnow, Thomas E},
      title        = {{A}lzheimer's {D}isease {R}isk {G}ene {SORL}1 {P}romotes
                      {R}eceptiveness of {H}uman {M}icroglia to
                      {P}ro-{I}nflammatory {S}timuli.},
      journal      = {Glia},
      volume       = {73},
      number       = {4},
      issn         = {0894-1491},
      address      = {Bognor Regis [u.a.]},
      publisher    = {Wiley-Liss},
      reportid     = {DZNE-2025-00335},
      pages        = {857 - 872},
      year         = {2025},
      abstract     = {Sorting protein-related receptor containing class A repeats
                      (SORLA) is an intracellular trafficking receptor encoded by
                      the Alzheimer's disease (AD) gene SORL1 (sortilin-related
                      receptor 1). Recent findings argue that altered expression
                      in microglia may underlie the genome-wide risk of AD seen
                      with some SORL1 gene variants, however, the functional
                      significance of the receptor in microglia remains poorly
                      explained. Using unbiased omics and targeted functional
                      analyses in iPSC-based human microglia, we identified a
                      crucial role for SORLA in sensitizing microglia to
                      pro-inflammatory stimuli. We show that SORLA acts as a
                      sorting factor for the pattern recognition receptor CD14,
                      directing CD14 exposure on the cell surface and priming
                      microglia to stimulation by pro-inflammatory factors. Loss
                      of SORLA in gene-targeted microglia impairs proper CD14
                      sorting and blunts pro-inflammatory responses. Our studies
                      indicate an important role for SORLA in shaping the
                      inflammatory brain milieu, a biological process important to
                      local immune responses in AD.},
      keywords     = {Microglia: drug effects / Humans / Microglia: metabolism /
                      Alzheimer Disease: genetics / Alzheimer Disease: metabolism
                      / Alzheimer Disease: pathology / LDL-Receptor Related
                      Proteins: genetics / LDL-Receptor Related Proteins:
                      metabolism / Membrane Transport Proteins: genetics /
                      Membrane Transport Proteins: metabolism / Lipopolysaccharide
                      Receptors: metabolism / Lipopolysaccharide Receptors:
                      genetics / Induced Pluripotent Stem Cells: metabolism /
                      Inflammation: metabolism / Inflammation: genetics / Cells,
                      Cultured / Alzheimer's disease (Other) / SORLA (Other) /
                      VPS10P domain receptors (Other) / brain inflammation (Other)
                      / microglia (Other) / SORL1 protein, human (NLM Chemicals) /
                      LDL-Receptor Related Proteins (NLM Chemicals) / Membrane
                      Transport Proteins (NLM Chemicals) / Lipopolysaccharide
                      Receptors (NLM Chemicals) / CD14 protein, human (NLM
                      Chemicals)},
      cin          = {AG Heppner},
      ddc          = {610},
      cid          = {I:(DE-2719)1810007},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39688327},
      pmc          = {pmc:PMC11845846},
      doi          = {10.1002/glia.24659},
      url          = {https://pub.dzne.de/record/276822},
}